Association between home smoking restrictions and changes in smoking behaviour among employed women.
Examine trends in home smoking restrictions among employed women not living alone and assess the associations of such restrictions with smoking behaviour. Multivariate logistic regression analysis of major demographic variables and household composition characteristics. 128 024 employed female respondents to the Census Bureau's current population survey over the 10 year period 1992 to 2002. The prevalence of smoke free homes has increased significantly over the past decade. This increase was evident across all demographic and household characteristics examined with the greatest rate of increase seen among smoking households. Nearly 90% of households consisting of all never smoking adult members reported having a smoke free home in 2001-02 compared with 22% of households consisting of all smokers. The extent of smoking restrictions in the home was the most powerful determinant of cessation of all the factors examined in the regression model. Odds of becoming a former smoker (any length) and quit for three months or more were seven to eight times greater among those women reporting their homes were smoke free compared with those whose homes permitted smoking anywhere in the home. Smoke free homes were associated with a highly significant increase in quitting (p<0.0001). However, at this time it is not clear what proportion of the observed effect can be attributed to living in a smoke free home. None the less, the significantly increased probability of quitting correlated with having a smoke free home found in this analysis, are substantially higher than the odds reported in most workplace studies published to date; additional studies are needed to elucidate this relation.


Comparative analysis of the 16S to 23S ribosomal intergenic spacer sequences of Bacillus thuringiensis strains and subspecies and of closely related species.
Bacillus thuringiensis spacer regions between the 16S and 23S rRNAs were amplified with conserved primers, designated 19-mer and 23-mer primers. A spacer region of 144 bp was determined for all of 6 B. thuringiensis strains, 7 B. thuringiensis subspecies, and 11 B. thuringiensis field isolates, as well as for the closely related species Bacillus cereus and Bacillus anthracis. Computer analysis and alignment of nucleotide sequences identified three mutations and one deletion in the intergenic spacer region (ISR) of B. thuringiensis subsp. kurstaki HD-1 when compared with ISR sequences from other subspecies. The same differences were identified between the ISR of B. thuringiensis strains and the ISR of B. cereus and B. anthracis. These minor differences do not seem to be sufficient to allow the design of a species-specific oligonucleotide probe.


Family health narratives: midlife women's concepts of vulnerability to illness.
Perceptions of vulnerability to illness are strongly influenced by the salience given to personal experience of illness in the family. This article proposes that this salience is created through autobiographical narrative, both as individual life story and collectively shaped family history. The article focuses on responses related to health in the family drawn from semi-structured interviews with women in a qualitative study exploring midlife women's health. Uncertainty about the future was a major emergent theme. Most respondents were worried about a specified condition such as heart disease or breast cancer. Many women were uncertain about whether illness in the family was inherited. Some felt certain that illness in the family meant that they were more vulnerable to illness or that their relatives' ageing would be mirrored in their own inevitable decline, while a few expressed cautious optimism about the future. In order to elucidate these responses, we focused on narratives in which family members' appearance was discussed and compared to that of others in the family. The visualization of both kinship and the effects of illness led to strong similarities being seen as grounds for worry. This led to some women distancing themselves from the legacies of illness in their families. Women tended to look at the whole family as the context for their perceptions of vulnerability, developing complex patterns of resemblance or difference within their families.


Bacterial sexually transmitted infections among HIV-infected patients in the United States: estimates from the Medical Monitoring Project.
Bacterial sexually transmitted infections may facilitate HIV transmission. Bacterial sexually transmitted infection testing is recommended for sexually active HIV-infected patients annually and more frequently for those at elevated sexual risk. We estimated percentages of HIV-infected patients in the United States receiving at least one syphilis, gonorrhea, or chlamydia test, and repeat (≥2 tests, ≥3 months apart) tests for any of these sexually transmitted infections from mid-2008 through mid-2010. The Medical Monitoring Project collects behavioral and clinical characteristics of HIV-infected adults receiving medical care in the United States using nationally representative sampling. Sexual activity included self-reported oral, vaginal, or anal sex in the past 12 months. Participants reporting more than 1 sexual partner or illicit drug use before/during sex in the past year were classified as having elevated sexual risk. Among participants with only 1 sex partner and no drug use before/during sex, those reporting consistent condom use were classified as low risk; those reporting sex without a condom (or for whom this was unknown) were classified as at elevated sexual risk only if they considered their sex partner to be a casual partner, or if their partner was HIV-negative or partner HIV status was unknown. Bacterial sexually transmitted infection testing was ascertained through medical record abstraction. Among sexually active patients, 55% were tested at least once in 12 months for syphilis, whereas 23% and 24% received at least one gonorrhea and chlamydia test, respectively. Syphilis testing did not vary by sex/sexual orientation. Receipt of at least 3 CD4+ T-lymphocyte cell counts and/or HIV viral load tests in 12 months was associated with syphilis testing in men who have sex with men (MSM), men who have sex with women only, and women. Chlamydia testing was significantly higher in sexually active women (30%) compared with men who have sex with women only (19%), but not compared with MSM (22%). Forty-six percent of MSM were at elevated sexual risk; 26% of these MSM received repeat syphilis testing, whereas repeat testing for gonorrhea and chlamydia was only 7% for each infection. Bacterial sexually transmitted infection testing among sexually active HIV-infected patients was low, particularly for those at elevated sexual risk. Patient encounters in which CD4+ T-lymphocyte cell counts and/or HIV viral load testing occurs present opportunities for increased bacterial sexually transmitted infection testing.


The natural compound oblongifolin C inhibits autophagic flux and enhances antitumor efficacy of nutrient deprivation.
Metabolic stress induces autophagy as an alternative source of energy and metabolites. Insufficient autophagy in nutrient-deprived cancer cells would be beneficial for cancer therapy. Here, we performed a functional screen in search of novel autophagy regulators from natural products. We showed that oblongifolin C (OC), a natural small molecule compound extracted from Garcinia yunnanensis Hu, is a potent autophagic flux inhibitor. Exposure to OC results in an increased number of autophagosomes and impaired degradation of SQSTM1/p62. Costaining of GFP-LC3B with LysoTracker Red or LAMP1 antibody demonstrates that autophagosome-lysosome fusion is blocked by OC treatment. Furthermore, OC inhibits lysosomal proteolytic activity by altering lysosomal acidification and downregulating the expression of lysosomal cathepsins. Importantly, OC can eliminate the tolerance of cancer cells to nutrient starvation. Starvation dramatically increases the susceptibility of cancer cells to OC-induced CASP3-dependent apoptosis in vitro. Subsequent studies in xenograft mouse model showed that OC has anticancer potency as revealed by increased staining of cleaved CASP3, LC3 puncta, and SQSTM1, as well as reduced expression of lysosomal cathepsins. Combined treatment with OC and caloric restriction potentiates anticancer efficacy of OC in vivo. Collectively, these data demonstrated that OC is a novel autophagic flux inhibitor and might be useful in anticancer therapy.


Loss of TIP1;1 aquaporin in Arabidopsis leads to cell and plant death.
Arabidopsis TIP1;1 (gammaTIP) is a member of the tonoplast family of aquaporins (AQP). Using RNA interference (RNAi) we reduced TIP1;1 to different extent in various lines. When most severely affected, miniature plants died, a phenotype partially complemented by the TIP1;1 homolog McMIP-F. Less severely affected lines produced small plants, early senescence, and showed lesion formation. The relative water content in TIP1;1 RNAi plants was not significantly affected. Global expression profiling suggested a disturbance in carbon metabolism in RNAi lines with upregulated transcripts for functions in carbon acquisition and respiration, vesicle transport, signaling and transcription, and radical oxygen stress. Metabolite profiles showed low glucose, fructose, inositol, and threonic, succinic, fumaric, and malic acids, but sucrose levels were similar to WT. Increased amounts were found for raffinose and several unknown compounds. TIP1;1 RNAi plants also contained high starch and apoplastic carbohydrate increased. A GFP-TIP1;1 fusion protein indicated tonoplast location in spongy mesophyll cells, and high signal intensity in palisade mesophyll associated with vesicles near plastids. Signals in vascular tissues were strongest not only in vesicle-like structures but also outlined large vacuoles. Compromised routing of carbohydrate and lack of sucrose provision for cell-autonomous functions seems to characterize this RNAi phenotype. We suggest a function for TIP1;1 in vesicle-based metabolite routing through or between pre-vacuolar compartments and the central vacuole. Phenotype and expression characteristics support a view of TIP1;1 functioning as a marker for vesicles that are targeted to the central vacuole.


Criminalization of medical error: who draws the line?
As stakeholders struggle to reconcile calls for accountability and pressures for increased patient safety, criminal prosecution of surgeons and other health-care workers for medical error seems to be on the rise. This paper examines whether legal systems can meaningfully draw a line between acceptable performance and negligence. By questioning essentialist assumptions behind 'crime' or 'negligence', this paper suggests that multiple overlapping and partially contradictory descriptions of the same act are always possible, and even necessary, to approximate the complexity of reality. Although none of these descriptions is inherently right or wrong, each description of the act (as negligence, or system failure, or pedagogical issue) has a fixed repertoire of responses and countermeasures appended to it, which enables certain courses of action while excluding others. Simply holding practitioners accountable (e.g. by putting them on trial) excludes any beneficial effects as it produces defensive posturing, obfuscation and excessive stress and leads to defensive medicine, silent reporting systems and interference with professional oversight. Calls for accountability are important, but accountability should be seen as bringing information about needed improvements to levels or groups that can do something about it, rather than deflecting resources into legal protection and limiting liability. We must avoid a future in which we have to turn increasingly to legal systems to wrong accountability out of practitioners because legal systems themselves have increasingly created a climate in which telling each other accounts openly is less and less possible.


An examination of participation in online gambling activities and the relationship with problem gambling.
Background and aims Online gambling participation is increasing rapidly, with relatively little research about the possible effects of different gambling activities on problem gambling behaviour. The aim of this exploratory study was to examine the participation in online gambling activities and the relationship with problem gambling among an international sample of online gamblers. Methods An online gambling survey was posted on 32 international gambling websites and resulted in 1,119 respondents over a four-month period. Results Poker was the most popular gambling activity online. A number of online activities were associated with problem gambling, including: roulette, poker, horse race betting, sports betting, spread betting and fruit (slot) machines. Not surprisingly, those that gambled on these activities regularly (except poker) were more likely to be a problem gambler, however, what is interesting is that the reverse is true for poker players; those that gambled regularly on poker were less likely to be a problem gambler compared to the non-regular poker players. The majority of the players also gambled offline, but there was no relationship between problem gambling and whether or not a person also gambled offline. Discussion Problem gambling is associated more with certain online gambling activities than others, and those gambling on two or more activities online were more likely to be a problem gambler. Conclusion This paper can help explain the impact different online gambling activities may have on gambling behaviour. Consideration needs to be given to the gambling activity when developing and implementing treatment programmes.


Comparison of Blood Pressure Control Rates Among Recommended Drug Selection Strategies for Initial Therapy of Hypertension.
Several approaches to initiation of antihypertensive therapy have been suggested. These include thiazide diuretics (TDs) as the first drug in all patients, initial drug selection based on age and race criteria, or therapy selection based on measures of plasma renin activity (PRA). It is uncertain which of these strategies achieves the highest control rate with monotherapy in Stage-I hypertension. We sought to compare control rates among these strategies. We used data from the Pharmacogenomic Evaluation of Antihypertensive Responses study (PEAR) to estimate control rates for each strategy: (i) TD for all, (ii) age- and race-based strategy: Hydrochlorothiazide (HCTZ) for all blacks and for whites ≥50 years and a renin-angiotensin system inhibitor (atenolol) for whites <50 years) or (iii) a PRA based strategy: HCTZ for suppressed PRA (<0.6ng/ml/h) and atenolol for non-suppressed PRA (≥0.6ng/ml/h) despite age or race. Hypertension was confirmed prior to treatment with HCTZ (148 blacks and 218 whites) or with atenolol (146 blacks and 221 whites). In the overall sample, using clinic blood pressure (BP) response, the renin-based strategy was associated with the greatest control rate (48.9% vs. 40.8% with the age and race-based strategy (P = 0.0004) and 31.7% with the TD for all strategy (P < 0.0001)). The findings were similar using home or by 24-hour ambulatory BP responses and within each racial subgroup. A strategy for selection of initial antihypertensive drug therapy based on PRA was associated with greater BP control rates compared to a thiazide-for-all or an age and race-based strategy.


Detoxification enzyme differences between a herbivorous and predatory mite.
The detoxification capabilities of the predatory mite Amblyseius fallacis and its herbivorous prey Tetranychus urticae are fundamentally different. The activities of mixed-function oxidase and trans-epoxide hydrolase are higher in the prey than in the predator; those of cis-epoxide hydrolase and glutathione transferase are lower; and esterase activity is similar. Dissimilarities may be related both to differing adaptations to plant allelochemicals and to the higher respiration rate of the predator. Hydrolytic and conjugating reactions appear more important than oxidative pathways in imparting organophosphate resistance to these acarines. These resistances provide insecticide selectivity favorable to the predator and improved integrated pest control.


Can We Assume the Gene Expression Profile as a Proxy for Signaling Network Activity?
Studying relationships among gene products by expression profile analysis is a common approach in systems biology. Many studies have generalized the outcomes to the different levels of central dogma information flow and assumed a correlation of transcript and protein expression levels. However, the relation between the various types of interaction (i.e., activation and inhibition) of gene products to their expression profiles has not been widely studied. In fact, looking for any perturbation according to differentially expressed genes is the common approach, while analyzing the effects of altered expression on the activity of signaling pathways is often ignored. In this study, we examine whether significant changes in gene expression necessarily lead to dysregulated signaling pathways. Using four commonly used and comprehensive databases, we extracted all relevant gene expression data and all relationships among directly linked gene pairs. We aimed to evaluate the ratio of coherency or sign consistency between the expression level as well as the causal relationships among the gene pairs. Through a comparison with random unconnected gene pairs, we illustrate that the signaling network is incoherent, and inconsistent with the recorded expression profile. Finally, we demonstrate that, to infer perturbed signaling pathways, we need to consider the type of relationships in addition to gene-product expression data, especially at the transcript level. We assert that identifying enriched biological processes via differentially expressed genes is limited when attempting to infer dysregulated pathways.


Public health surveillance in the UK revolutionises our understanding of the invasive Salmonella Typhimurium epidemic in Africa.
The ST313 sequence type of Salmonella Typhimurium causes invasive non-typhoidal salmonellosis and was thought to be confined to sub-Saharan Africa. Two distinct phylogenetic lineages of African ST313 have been identified. We analysed the whole genome sequences of S. Typhimurium isolates from UK patients that were generated following the introduction of routine whole-genome sequencing (WGS) of Salmonella enterica by Public Health England in 2014. We found that 2.7% (84/3147) of S. Typhimurium from patients in England and Wales were ST313 and were associated with gastrointestinal infection. Phylogenetic analysis revealed novel diversity of ST313 that distinguished UK-linked gastrointestinal isolates from African-associated extra-intestinal isolates. The majority of genome degradation of African ST313 lineage 2 was conserved in the UK-ST313, but the African lineages carried a characteristic prophage and antibiotic resistance gene repertoire. These findings suggest that a strong selection pressure exists for certain horizontally acquired genetic elements in the African setting. One UK-isolated lineage 2 strain that probably originated in Kenya carried a chromosomally located bla CTX-M-15, demonstrating the continual evolution of this sequence type in Africa in response to widespread antibiotic usage. The discovery of ST313 isolates responsible for gastroenteritis in the UK reveals new diversity in this important sequence type. This study highlights the power of routine WGS by public health agencies to make epidemiologically significant deductions that would be missed by conventional microbiological methods. We speculate that the niche specialisation of sub-Saharan African ST313 lineages is driven in part by the acquisition of accessory genome elements.


Investigating the ferric ion binding site of magnetite biomineralisation protein Mms6.
The biomineralization protein Mms6 has been shown to be a major player in the formation of magnetic nanoparticles both within the magnetosomes of magnetotactic bacteria and as an additive in synthetic magnetite precipitation assays. Previous studies have highlighted the ferric iron binding capability of the protein and this activity is thought to be crucial to its mineralizing properties. To understand how this protein binds ferric ions we have prepared a series of single amino acid substitutions within the C-terminal binding region of Mms6 and have used a ferric binding assay to probe the binding site at the level of individual residues which has pinpointed the key residues of E44, E50 and R55 involved in Mms6 ferric binding. No aspartic residues bound ferric ions. A nanoplasmonic sensing experiment was used to investigate the unstable EER44, 50,55AAA triple mutant in comparison to native Mms6. This suggests a difference in interaction with iron ions between the two and potential changes to the surface precipitation of iron oxide when the pH is increased. All-atom simulations suggest that disruptive mutations do not fundamentally alter the conformational preferences of the ferric binding region. Instead, disruption of these residues appears to impede a sequence-specific motif in the C-terminus critical to ferric ion binding.


Neurovascular coupling in the mammalian brain.
Normal brain function requires proper supply of oxygen and glucose in a timely and local manner. This is achieved through an orchestrated intercellular communication between neurones, astrocytes and microvessels that results in a rapid and restricted increase in cerebral blood flow, a process known as neurovascular coupling. Astrocytic end-feet make close contacts with neuronal synapses and blood vessels and, given their ability to release vasoactive signals following neuronal activation, have been recognized as key intermediaries in the neurovascular response. Both dilating and constricting signals appear to be released from astrocytes upon increases in intracellular Ca(2+) concentration, and both dilatation and constriction of brain vessels have been observed in previous studies. In this article, we discuss the various astrocyte-derived vasodilating and vasoconstricting signals, their interactions and effects on astrocytes and vascular smooth muscle cells, and suggest the importance of the intrinsic properties of the latter cell type on the overall neurovascular response. We present a working model in which the rise in astrocytic Ca(2+) following neuronal activation leads not only to the rapid activation of calcium-activated K(+) channels in astrocytic end-feet, but also to their modulation by metabolites of the arachidonic acid pathway, which in general have been proposed to act on vascular smooth muscle cells rather than on astrocytes. We propose that this latter mechanism may in turn modulate K(+) signalling from astrocytes to smooth muscle cells, influencing the overall effects of the vasodilating and vasoconstricting signals released during neuronal activation.


Evaluation of Factors Associated with Sexual Function in Infertile Women.
Infertility is a major and problem influencing different aspects of couples life, especially those of women. Sexual dysfunction is the silent partner of infertility. This study aimed to identify the above-mentioned factors to make necessary decisions and perform efficient interventions to improve the sexual health of infertile women. This study investigated the factors influencing sexual dysfunction in infertile women in Mashhad, Iran. This cross-sectional study was conducted on 85 infertile women visiting governmental Infertility Clinic and Research Center in Mashhad, Iran. The convenience sampling method was used in this study. The research tools included a demographic and infertility information form, a sexual self-efficacy questionnaire based on Schwarzer's General Self-Efficacy Scale, Female Sexual Function Index (FSFI), and Evaluation and Nurturing Relationship Issues, Communication, and Happiness (ENRICH) Marital Satisfaction Scale. The descriptive statistical tests and logistic regression method were used to analyze data. The mean age of women was 31.18 ± 5.56 years old. The majority of participants (36.7%) had higher educations, and 60% of them were housewives. Most of their husbands (49.4%) were self-employed. The mean period of infertility awareness was 6.02 ± 4.47 years, and the mean period of infertility treatment was 4.11 ± 4.46 years. The following variables influenced the sexual function of infertile women: sexual self-efficacy, sexual satisfaction, marital satisfaction, the educational level of both wife and husband, income, satisfaction with spouse appearance, and the high costs of infertility treatment. The findings indicated that some factors such as sexual self-efficacy, marital satisfaction, sexual satisfaction, education, and cost of infertility treatment are associated with sexual function in infertile women.


Residue-Level Allostery Propagates through the Effective Coarse-Grained Hessian.
The long-ranged coupling between residues that gives rise to allostery in a protein is built up from short-ranged physical interactions. Computational tools used to predict this coupling and its functional relevance have relied on the application of graph theoretical metrics to residue-level correlations measured from all-atom molecular dynamics simulations. The short-ranged interactions that yield these long-ranged residue-level correlations are quantified by the effective coarse-grained Hessian. Here we compute an effective harmonic coarse-grained Hessian from simulations of a benchmark allosteric protein, IGPS, and demonstrate the improved locality of this graph Laplacian over two other connectivity matrices. Additionally, two centrality metrics are developed that indicate the direct and indirect importance of each residue at producing the covariance between the effector binding pocket and the active site. The residue importance indicated by these two metrics is corroborated by previous mutagenesis experiments and leads to unique functional insights; in contrast to previous computational analyses, our results suggest that fP76-hK181 is the most important contact for conveying direct allosteric paths across the HisF-HisH interface. The connectivity around fD98 is found to be important at affecting allostery through indirect means.


Notch signaling regulates tubular morphogenesis during repair from biliary damage in mice.
Repair from biliary damages requires the biliary specification of hepatic progenitor cells and the remodeling of ductular reactive structures into branching biliary tubules. We hypothesized that the morphogenetic role of Notch signaling is maintained during the repair process and have addressed this hypothesis using pharmacologic and genetic models of defective Notch signaling. Treatment with DDC (3,5-diethoxycarbonyl-1,4-dihydrocollidine) or ANIT (alpha-naphthyl-isothiocyanate) was used to induce biliary damage in wild type mice and in mice with a liver specific defect in the Notch-2 receptor (Notch-2-cKO) or in RPB-Jk. Hepatic progenitor cells, ductular reaction, and mature ductules were quantified using K19 and SOX-9. In DDC treated wild type mice, pharmacologic Notch inhibition with dibenzazepine decreased the number of both ductular reaction and hepatic progenitor cells. Notch-2-cKO mice treated with DDC or ANIT accumulated hepatic progenitor cells that failed to progress into mature ducts. In RBP-Jk-cKO mice, mature ducts and hepatic progenitor cells were both significantly reduced with respect to similarly treated wild type mice. The mouse progenitor cell line BMOL cultured on matrigel, formed a tubular network allowing the study of tubule formation in vitro; γ-secretase inhibitor treatment and siRNAs silencing of Notch-1, Notch-2 or Jagged-1 significantly reduced both the length and number of tubular branches. These data demonstrate that Notch signaling plays an essential role in biliary repair. Lack of Notch-2 prevents biliary tubule formation, both in vivo and in vitro. Lack of RBP-Jk inhibits the generation of biliary-committed precursors and tubule formation.


Anaphylaxis induced by lentil inhalation.
Anaphylaxis is a rapid onset serious allergic reaction which may be fatal. Foods are the most common allergens leading to anaphylaxis especially for childhood. Most of the food-induced anaphylactic reactions take place after ingestion of the allergic food and only a few cases exist with anaphylactic reactions induced by inhalation of foods such as peanut, soybean and lupine. The case we present is unusual in that an 8 1/2-year-old boy developed anaphylaxis with the inhalation of steam from boiling lentils.


High doses of riboflavin and the elimination of dietary red meat promote the recovery of some motor functions in Parkinson's disease patients.
Abnormal riboflavin status in the absence of a dietary deficiency was detected in 31 consecutive outpatients with Parkinson's disease (PD), while the classical determinants of homocysteine levels (B6, folic acid, and B12) were usually within normal limits. In contrast, only 3 of 10 consecutive outpatients with dementia without previous stroke had abnormal riboflavin status. The data for 12 patients who did not complete 6 months of therapy or did not comply with the proposed treatment paradigm were excluded from analysis. Nineteen PD patients (8 males and 11 females, mean age +/- SD = 66.2+/-8.6 years; 3, 3, 2, 5, and 6 patients in Hoehn and Yahr stages I to V) received riboflavin orally (30 mg every 8 h) plus their usual symptomatic medications and all red meat was eliminated from their diet. After 1 month the riboflavin status of the patients was normalized from 106.4+/-34.9 to 179.2+/-23 ng/ml (N = 9). Motor capacity was measured by a modification of the scoring system of Hoehn and Yahr, which reports motor capacity as percent. All 19 patients who completed 6 months of treatment showed improved motor capacity during the first three months and most reached a plateau while 5/19 continued to improve in the 3- to 6-month interval. Their average motor capacity increased from 44 to 71% after 6 months, increasing significantly every month compared with their own pretreatment status (P < 0.001, Wilcoxon signed rank test). Discontinuation of riboflavin for several days did not impair motor capacity and yellowish urine was the only side effect observed. The data show that the proposed treatment improves the clinical condition of PD patients. Riboflavin-sensitive mechanisms involved in PD may include glutathione depletion, cumulative mitochondrial DNA mutations, disturbed mitochondrial protein complexes, and abnormal iron metabolism. More studies are required to identify the mechanisms involved.


Anaerobic fermentation of glycerol: a platform for renewable fuels and chemicals.
To ensure the long-term viability of biorefineries, it is essential to go beyond the carbohydrate-based platform and develop complementing technologies capable of producing fuels and chemicals from a wide array of available materials. Glycerol, a readily available and inexpensive compound, is generated during biodiesel, oleochemical, and bioethanol production processes, making its conversion into value-added products of great interest. The high degree of reduction of carbon atoms in glycerol confers the ability to produce fuels and reduced chemicals at higher yields when compared to the use of carbohydrates. This review focuses on current engineering efforts as well as the challenges involved in the utilization of glycerol as a carbon source for the production of fuels and chemicals.


The regulation of nuclear membrane permeability by Ca2+ signaling: a tightly regulated pore or a floodgate?
The nuclear pore complex functions both to separate and to connect the nucleus and the cytoplasm. Minute-to-minute changes in gene expression depend on rapid translocation of transcription factors and other regulatory proteins from the cytosol into the nucleus. However, a controversy exists as to whether cell signaling allows large molecules to enter the nucleus through tightly regulated facilitated transport or by the opening of a floodgate. A recent report suggesting that some hormones increase nuclear permeability through changes in intracellular Ca(2+) concentration has reignited this debate. Here, I consider both the basic permeability of the nuclear membrane under resting conditions and the effects of Ca(2+) on the permeability of the nuclear pore. I discuss facilitated transport through the nuclear pore complex, with particular attention to the nuclear transport of Ca(2+)-CaM signaling complexes. Finally, I weigh the arguments in favor of a generic increase in permeability versus stimulation of facilitated transport as possible mechanisms for mediating cell signaling to the nucleus.


At5PTase13 modulates cotyledon vein development through regulating auxin homeostasis.
Phosphatidylinositol signaling pathway and the relevant metabolites are known to be critical to the modulation of different aspects of plant growth, development, and stress responses. Inositol polyphosphate 5-phosphatase is a key enzyme involved in phosphatidylinositol metabolism and is encoded by an At5PTase gene family in Arabidopsis thaliana. A previous study shows that At5PTase11 mediates cotyledon vascular development probably through the regulation of intracellular calcium levels. In this study, we provide evidence that At5PTase13 modulates the development of cotyledon veins through its regulation of auxin homeostasis. A T-DNA insertional knockout mutant, At5pt13-1, showed a defect in development of the cotyledon vein, which was rescued completely by exogenous auxin and in part by brassinolide, a steroid hormone. Furthermore, the mutant had reduced auxin content and altered auxin accumulation in seedlings revealed by the DR5:beta-glucuronidase fusion construct in seedlings. In addition, microarray analysis shows that the transcription of key genes responsible for auxin biosynthesis and transport was altered in At5pt13-1. The At5pt13-1 mutant was also less sensitive to auxin inhibition of root elongation. These results suggest that At5PTase13 regulates the homeostasis of auxin, a key hormone controlling vascular development in plants.


Evidence for the involvement of p59fyn and p53/56lyn in collagen receptor signalling in human platelets.
The binding of collagen to platelet glycoprotein VI (GPVI) leads to the subsequent activation of phospholipase Cgamma2 through a pathway that is dependent on the Fc receptor gamma (FcR gamma) chain and the tyrosine kinase p72syk. We have investigated the role of platelet Src-family kinases in this signalling pathway. The selective Src-family kinase inhibitor PP1 prevented collagen-stimulated increases in whole-cell tyrosine phosphorylation and tyrosine phosphorylation of the FcR gamma chain and p72syk. A similar set of observations was made for a collagen-related peptide (CRP), which binds to GPVI but not to the integrin alpha2beta1 (GPIa/IIa). These effects were seen at a concentration of PP1 that inhibited platelet aggregation, dense granule release and Ca2+ mobilization induced by CRP, but not aggregation and Ca2+ mobilization mediated by the G-protein-coupled receptor agonist thrombin. After stimulation by CRP or collagen, the Src-family kinases p59fyn and p53/56lyn became associated with several tyrosine-phosphorylated proteins including the FcR gamma chain. This was not true of the other platelet Src-family kinases. The association between the FcR gamma chain and p59fyn was also seen under basal conditions, and was stable only in the weak detergent Brij96 but not in Nonidet P40, suggesting a non-SH2-dependent interaction. These results provide strong evidence for the involvement of p59fyn and p53/56lyn in signalling via GPVI, with p59fyn possibly acting upstream of FcR gamma chain phosphorylation.


Tularemia: current diagnosis and treatment options.
Tularemia is an infection caused by Francisella tularensis with a worldwide distribution and diverse clinical manifestations. Limitations in both culture and serologic testing have led to substantial research into new diagnostic techniques and their clinical application, with PCR testing as the best example. This review focuses on the utility of culture, PCR and serologic testing for tularemia. In addition, we also review the evidence to support different therapeutic options for tularemia, highlighting both the most effective supporting evidence for therapeutic recommendations as well as gaps in current knowledge. We conclude the article with suggestions regarding potential areas for future research.


Enhanced inhibition of prostate cancer xenograft tumor growth by combining quercetin and green tea.
The chemopreventive activity of green tea (GT) is limited by the low bioavailability and extensive methylation of GT polyphenols (GTPs) in vivo. We determined whether a methylation inhibitor quercetin (Q) will enhance the chemoprevention of prostate cancer in vivo. Androgen-sensitive LAPC-4 prostate cancer cells were injected subcutaneously into severe combined immunodeficiency (SCID) mice one week before the intervention. The concentration of GTPs in brewed tea administered as drinking water was 0.07% and Q was supplemented in diet at 0.2% or 0.4%. After 6-weeks of intervention tumor growth was inhibited by 3% (0.2% Q), 15% (0.4% Q), 21% (GT), 28% (GT+0.2% Q) and 45% (GT+0.4% Q) compared to control. The concentration of non-methylated GTPs was significantly increased in tumor tissue with GT+0.4% Q treatment compared to GT alone, and was associated with a decreased protein expression of catechol-O-methyltransferase and multidrug resistance-associated protein (MRP)-1. The combination treatment was also associated with a significant increase in the inhibition of proliferation, androgen receptor and phosphatidylinositol 3-kinase/Akt signaling, and stimulation of apoptosis. The combined effect of GT+0.4% Q on tumor inhibition was further confirmed in another experiment where the intervention started prior to tumor inoculation. These results provide a novel regimen by combining GT and Q to improve chemoprevention in a non-toxic manner and warrant future studies in humans.


An application of collaborative targeted maximum likelihood estimation in causal inference and genomics.
A concrete example of the collaborative double-robust targeted likelihood estimator (C-TMLE) introduced in a companion article in this issue is presented, and applied to the estimation of causal effects and variable importance parameters in genomic data. The focus is on non-parametric estimation in a point treatment data structure. Simulations illustrate the performance of C-TMLE relative to current competitors such as the augmented inverse probability of treatment weighted estimator that relies on an external non-collaborative estimator of the treatment mechanism, and inefficient estimation procedures including propensity score matching and standard inverse probability of treatment weighting. C-TMLE is also applied to the estimation of the covariate-adjusted marginal effect of individual HIV mutations on resistance to the anti-retroviral drug lopinavir. The influence curve of the C-TMLE is used to establish asymptotically valid statistical inference. The list of mutations found to have a statistically significant association with resistance is in excellent agreement with mutation scores provided by the Stanford HIVdb mutation scores database.


NFBD1, like 53BP1, is an early and redundant transducer mediating Chk2 phosphorylation in response to DNA damage.
Signaling pathways in response to DNA double strand breaks involve molecular cascades consisting of sensors, transducers, and effector proteins that activate cell cycle checkpoints and recruit repair machinery proteins. NFBD1 (a nuclear factor with BRCT domains protein 1) contains FHA (forkhead-associated), BRCT (breast cancer susceptibility gene 1 carboxyl terminus) domains, and internal repeats and is an early participant in nuclear foci in response to IR. To elucidate its role in the response pathways, small interfering RNA (siRNA) directed against NFDB1 in human cells demonstrated that its absence is associated with increased radio-sensitivity and delayed G(2)/M transition, but not G(1) to S. NFBD1 associates with nuclear foci within minutes following IR, a property similar to histone H2AX, 53BP1, and Chk2, which are all early participants in the DNA damage signaling cascade. Temporal studies show that H2AX is required for the foci positive for NFBD1, but NFBD1 is not needed for 53BP1- and H2AX-positive foci. NFBD1, together with 53BP1, plays a partially redundant role in regulating phosphorylation of the downstream effector protein, Chk2, since abrogation of both diminishes phosphorylated Chk2 in IR-induced foci. These results place NFBD1 parallel to 53BP1 in regulating Chk2 and downstream of H2AX in the recruitment of repair and signaling proteins to sites of DNA damage.


A community study of delay in presenting with signs of melanoma to medical practitioners.
In the absence of more effective treatment for advanced tumors, early diagnosis and treatment of localized tumors is the most effective way of reducing the burden of illness associated with melanoma. This study examined the following factors: prevalence of signs of melanoma (a mole changing in size, shape, appearance, or color, itching or tingling, bleeding or weeping, becoming raised) in 1344 individuals in a randomly selected sample of 1075 households; the length of delay in seeking medical advice; the factors associated with either going to a medical practitioner or not going/delaying; and the actions of the medical practitioners when first presented with these signs. The results indicate that a large proportion of the sample (11.9%, n = 156) had observed signs of melanoma in the previous 12 months. Of the sample reporting signs that had first appeared in the previous 5 years, only 32% sought medical advice about the signs within the recommended period. Of the sample either not seeking advice at all or delaying, 49% reported that they thought the sign "wasn't serious/would clear up." Furthermore, 30% of the sample either did not known or underrated the importance of early detection and treatment of lesions. These results indicate that there is a deficit in the knowledge of the general public about the signs of melanoma, the severity of the disease, and the possible risks associated with delay.


What is the source of chronic low back pain and does age play a role?
The objective of this study was to estimate the prevalence, mean age, and association of prevalence and age of lumbar internal disc disruption (IDD), facet joint pain (FJP), sacroiliac joint pain (SIJP), spinal and pelvic insufficiency fractures, interspinous ligament injury/Baastrup's Disease, and soft tissue irritation by fusion hardware. The study's design was a retrospective chart review. The study was set in an academic spine center. A total of 378 cases from 358 patients were reviewed of which 170 cases from 156 patients who underwent diagnostic procedures were included. Discography, dual diagnostic facet joint blocks, intra-articular sacroiliac joint injections, anesthetic injections of painful interspinous ligaments/opposing spinous processes/posterior fusion hardware, or percutaneous augmentation were performed. Prevalence and age were analyzed for each diagnosis group. Patients with recalcitrant low back pain underwent diagnostic procedures based on their clinical presentation until the pain source was identified. The prevalence of internal disc disruption, facet joint pain and sacroiliac joint pain was 42%, 31%, and 18%, respectively. Patients with internal disc disruption were significantly younger than those with facet joint pain or sacroiliac joint pain. Increased age was associated with a decreased probability of internal disc disruption and increased probabilities of facet joint pain and sacroiliac joint pain as the source of low back pain until approximately age 70. Our data confirm the intervertebral disc as the most common etiology of chronic low back pain in adults. Based on our sample, the younger the patient, the more likely low back pain is discogenic in origin. Facetogenic or sacroiliac joint pain is more likely in older patients.


Pattern and rate of progression of periodontal attachment loss in an urban population of South Brazil: a 5-years population-based prospective study.
The aim of this 5-years longitudinal study was to investigate the pattern and rate of periodontal attachment loss (PAL) progression in an urban population in South Brazil. In 2001, a multistage probability sampling strategy was used to derive a representative sample of 1,465 dentate individuals from Porto Alegre, Brazil. Five years later, 697 dentate individuals (294M/403F, mean age: 37.9 ± 13.3) were available for follow-up. PAL was assessed by calibrated examiners using a full-mouth protocol. Estimates of proximal PAL progression and standard errors (SE) are reported. Fifty-six per cent (SE: 1.9) and 36% (SE: 1.8) of subjects showed PAL progression ≥3 mm affecting ≥2 and ≥4 teeth respectively. PAL progression ≥3 mm was mostly localized affecting 3.8 (SE: 0.2) teeth and 5.7 (SE: 0.3) sites. Annual PAL progression was, on average, 0.3 mm (SE: 0.01). Significant differences in PAL progression were observed according to age, gender, race and socioeconomic status. PAL progression increased with age reaching the highest progression rate in the 40-49 years cohort, and then decreased in older age groups. PAL progression was consistently higher among males and non-Whites than females and whites. A large proportion of this urban Brazilian sample was affected by PAL progression underscoring the need for health promotion initiatives aiming at preventing progression of destructive periodontal disease.


Effect of spurious diffraction orders in arbitrary multifoci patterns produced via phase-only holograms.
We analyze the effect of spurious diffraction orders when generating functional multifoci patterns produced by illuminating a phase-only hologram with a single Gaussian beam. Using a practical device for encoding a hologram generates an undesirable zero order and high-diffraction orders at the Fourier plane. This translates to the fact that a significant fraction of the incident light does not necessarily convert to functional multifoci patterns. In most applications, the zero order can be avoided by generating foci patterns shifted off the optical axis, which further increases the amount of light distributed to spurious high-diffraction orders owing to the reduction of light directed to the desired foci pattern. We analyze the amount of light dispersed to spurious orders and show that these unwanted orders can be a major limiting factor for most applications based on arbitrary multifoci patterns.


Vertical transport and sinks of perfluoroalkyl substances in the global open ocean.
The ubiquitous occurrence of perfluoroalkyl substances (PFAS) in the open ocean has been previously documented, but their vertical transport and oceanic sinks have not been comprehensively characterized and quantified at the oceanic scale. During the Malaspina 2010 circumnavigation expedition, 21 PFAS were measured at the surface and at the deep chlorophyll maximum (DCM) in the Atlantic, Indian and Pacific oceans. In this work, we report an extended data set of PFAS dissolved phase concentrations at the DCM. ∑PFAS at the DCM varied from 130 to 11 000 pg L-1, with a global average value of 500 pg L-1. Perfluorooctanesulfonate (PFOS) abundance contributed 39% of ∑PFAS, followed by perfluorodecanoate (PFDA, 17%), and perfluorohexanoate (PFHxA, 12%). The relative contribution of the remaining compounds was below 10%, with perfluorooctanoate (PFOA) contributing only 5% to PFAS measured at the DCM. Estimates of vertical diffusivity, derived from microstructure turbulence observations in the upper (<300 m) water column, allowed the derivation of PFAS eddy diffusive fluxes from concurrent field measurements of eddy diffusivity and PFAS concentrations. The PFAS concentrations at the DCM predicted from an eddy diffusivity model were lower than field-measured concentrations, suggesting a relevant role of other vertical transport mechanisms. Settling fluxes of organic matter bound PFAS (biological pump), oceanic circulation and potential, yet un-reported, biological transformations are discussed.


Surgeon subspecialty as a factor in improving long-term outcomes for gastric cancer: Twenty years of experience in Korea.
The results of gastric cancer treatment have improved during the past 2 decades. In addition to early diagnosis, surgeon experience and subspecialty may influence long-term outcomes. This study analyzed data accumulated during the past 20 years regarding the impact of surgical subspecialty on gastric cancer prognosis. A 20-year, retrospective study. Korea University Guro Hospital, Seoul. A total of 2797 patients admitted between 1984 and 2003 with surgically treated, pathologically confirmed, primary gastric adenocarcinoma. Long-term survival. The incidence of total gastrectomy and the number of retrieved lymph nodes increased during the study period. In curative cases, 5-year survival improved from 66.1% to 76.6%, and this survival gain was restricted to stages I, III, and IV. A Cox proportional hazards regression model showed that age, sex, tumor location, type of resection, stage, and the interaction between period of study and surgical subspecialty were independent prognostic factors. This large, long-term cohort study demonstrates that the management of gastric cancer has been largely successful, with favorable trends in prognostic factors. Successful outcomes are realized more often by gastric surgical specialists. Efforts must be made to improve the treatment of patients with stage II gastric cancer because the improvements in long-term results have plateaued.


Ideal-observer detectability in photon-counting differential phase-contrast imaging using a linear-systems approach.
To provide a cascaded-systems framework based on the noise-power spectrum (NPS), modulation transfer function (MTF), and noise-equivalent number of quanta (NEQ) for quantitative evaluation of differential phase-contrast imaging (Talbot interferometry) in relation to conventional absorption contrast under equal-dose, equal-geometry, and, to some extent, equal-photon-economy constraints. The focus is a geometry for photon-counting mammography. Phase-contrast imaging is a promising technology that may emerge as an alternative or adjunct to conventional absorption contrast. In particular, phase contrast may increase the signal-difference-to-noise ratio compared to absorption contrast because the difference in phase shift between soft-tissue structures is often substantially larger than the absorption difference. We have developed a comprehensive cascaded-systems framework to investigate Talbot interferometry, which is a technique for differential phase-contrast imaging. Analytical expressions for the MTF and NPS were derived to calculate the NEQ and a task-specific ideal-observer detectability index under assumptions of linearity and shift invariance. Talbot interferometry was compared to absorption contrast at equal dose, and using either a plane wave or a spherical wave in a conceivable mammography geometry. The impact of source size and spectrum bandwidth was included in the framework, and the trade-off with photon economy was investigated in some detail. Wave-propagation simulations were used to verify the analytical expressions and to generate example images. Talbot interferometry inherently detects the differential of the phase, which led to a maximum in NEQ at high spatial frequencies, whereas the absorption-contrast NEQ decreased monotonically with frequency. Further, phase contrast detects differences in density rather than atomic number, and the optimal imaging energy was found to be a factor of 1.7 higher than for absorption contrast. Talbot interferometry with a plane wave increased detectability for 0.1-mm tumor and glandular structures by a factor of 3-4 at equal dose, whereas absorption contrast was the preferred method for structures larger than ∼0.5 mm. Microcalcifications are small, but differ from soft tissue in atomic number more than density, which is favored by absorption contrast, and Talbot interferometry was barely beneficial at all within the resolution limit of the system. Further, Talbot interferometry favored detection of "sharp" as opposed to "smooth" structures, and discrimination tasks by about 50% compared to detection tasks. The technique was relatively insensitive to spectrum bandwidth, whereas the projected source size was more important. If equal photon economy was added as a restriction, phase-contrast efficiency was reduced so that the benefit for detection tasks almost vanished compared to absorption contrast, but discrimination tasks were still improved close to a factor of 2 at the resolution limit. Cascaded-systems analysis enables comprehensive and intuitive evaluation of phase-contrast efficiency in relation to absorption contrast under requirements of equal dose, equal geometry, and equal photon economy. The benefit of Talbot interferometry was highly dependent on task, in particular detection versus discrimination tasks, and target size, shape, and material. Requiring equal photon economy weakened the benefit of Talbot interferometry in mammography.


A model for predicting chronic TMD: practical application in clinical settings.
Substantial cost is associated with the treatment of chronic temporomandibular disorders, or TMDs, and patients with TMDs often experience significant psychosocial distress. Early intervention based on identified risk factors has potential financial and functional benefits. Two hundred four patients with acute TMD were evaluated via an assessment battery that included physical, psychological and social measures. All participants were diagnosed as having TMD on the basis of the research diagnostic criteria for TMD, Axis I. At the six-month follow-up assessment, patients were considered to have chronic TMD if they continued to have TMD pain. This resulted in 144 of the patients being classified in the chronic group and 60 being classified in the nonchronic group. A comparison of the acute TMD data demonstrated that the group that went on to develop chronic TMD and the group that did not differed significantly in their scores on numerous biopsychosocial indexes. Although several biopsychosocial measures were found to differentiate these two groups before the onset of chronic TMD, logistic regression analysis demonstrated that a two-variable predictive model consisting of the presence of a muscle disorder and characteristic pain intensity (that is, the mean of these three ratings: patient's report of current pain, worst pain in the last three months and mean pain in the last three months) accurately classified 91 percent of the subjects who went on to develop chronic TMD. During the acute phase of TMD, two variables allowed for an accurate prediction rate of 91 percent among patients who went on to develop chronic TMD. This model provides clinicians with the opportunity to identify at-risk patients early and initiate adjunctive or alternative treatments, thus reducing the likelihood of the development of TMD chronicity.


Changes in abortion rates between 2000 and 2008 and lifetime incidence of abortion.
To estimate abortion rates among subpopulations of women in 2008, assess changes in subpopulation abortion rates since 2000, and estimate the lifetime incidence of abortion. We combined secondary data from several sources, including the 2008 Abortion Patient Survey, the Current Population Surveys for 2008 and 2009, and the 2006-2008 National Survey of Family Growth, to estimate abortion rates by subgroup and lifetime incidence of abortion for U.S. women of reproductive age. The abortion rate declined 8.0% between 2000 and 2008, from 21.3 abortions per 1,000 women aged 15-44 to 19.6 per 1,000. Decreases in abortion were experienced by most subgroups of women. One notable exception was poor women; this group accounted for 42.4% of abortions in 2008, and their abortion rate increased 17.5% between 2000 and 2008 from 44.4 to 52.2 abortions per 1,000. In addition to poor women, abortion rates were highest for women who were cohabiting (52.0 per 1,000), aged 20-24 (39.9 per 1,000), or non-Hispanic African American (40.2 per 1,000). If the 2008 abortion rate prevails, 30.0% of women will have an abortion by age 45. Abortion is becoming increasingly concentrated among poor women, and restrictions on abortion disproportionately affect this population.


Haematological support of high-dose sequential chemotherapy: clinical evidence for reduction of toxicity and high response rates in poor risk lymphomas.
The toxicity and feasibility of a high-dose sequential (HDS) chemotherapy programme delivered with growth factor support were evaluated in patients with intermediate and high-grade non-Hodgkin's lymphoma (NHL) or with progressive Hodgkin's disease. The scheme includes the sequential administration of single cytotoxic drugs at very high doses followed by intensified treatment with circulating progenitor autograft. In some instances, the original HDS scheme, initially designed at the Milan Cancer Center, was partially modified and intensified with a preliminary debulking phase. The use of G-CSF (filgrastim) made toxicity in the high-dose phase acceptable and allowed good harvests of peripheral blood progenitor cells (PBPC); the use of PBPC in the final autografting phase resulted in low haematological toxicity. Of 71 patients with NHL treated at our institution with either the original or the intensified HDS version, the overall toxicity-related mortality was 5.6%, thus comparable to lethal toxicity commonly associated with conventional chemotherapy. Adequate PBPC harvests are crucial for good tolerability of the programme. Optimal harvests are generally obtained in patients without neoplastic marrow infiltration while patients with marrow disease often have a poorer mobilisation. However, an optimally time-spaced chemotherapy debulking might also restore sufficient mobilisation in these latter patients. In terms of therapeutic efficacy, HDS had produced promising results since the initial experience in relapsed patients. More recently, HDS was evaluated as first-line treatment in a series of 22 consecutive patients, presenting with advanced-stage, intermediate-grade NHL other than diffuse large cell subtype. A CR rate of 82% was obtained following HDS, with a projected survival of 86% at five years. Thus, delivery of an intensive high-dose chemotherapy programme with haematopoietic growth factor support was found to be feasible and reasonably safe. The high anti-tumour efficacy of such a scheme makes it suitable for wider applicability in all those chemosensitive tumours where a dose increase might enhance the chance of cure.


Sputum induction for the diagnosis of tuberculosis.
Confirmation of tuberculosis in young children is difficult as they seldom expectorate sputum. Gastric aspirates are invasive and stressful and like laryngeal swabs are seldom smear positive. Induction of sputum by nebulised hypertonic saline (3%) was attempted in 30 Malawian children aged 3-15 years and was successful in 29. Four sputa were smear positive and Mycobacterium tuberculosis was cultured from three of them. A further four sputa were culture positive though smear negative. In all, the diagnosis of tuberculosis was confirmed in eight (28%) of 29 children. The presence of polymorphonuclear cells in the specimen was indicative of sputum, in contrast to epithelial cells which originate from saliva. A predominance of polymorphonuclear cells in specimens was more common in older children and these specimens were more likely to be smear positive or culture positive. Sputum induction is a useful method for the confirmation of tuberculosis and is possible in young children.


Total ankle arthroplasty versus ankle arthrodesis for the treatment of end-stage ankle arthritis: a meta-analysis of comparative studies.
Total ankle arthroplasty (TAA) and ankle arthrodesis (AA) are the main surgical treatment options for end-stage ankle arthritis. Although the superiority of each modality remains debated, there remains a lack of high-quality evidence-based studies, such as randomized controlled clinical trials, and meta-analyses of comparative studies. We performed a meta-analysis of comparative studies to determine whether there is a significant difference between these two procedures in terms of (i) clinical scores and patient satisfaction, (ii) re-operations, and (iii) complications. We conducted a comprehensive search in the MEDLINE, EMBASE, and Cochrane library databases. Only retrospective or prospective comparative studies were included in this meta-analysis. The literature search, data extraction, and quality assessment were conducted by two independent reviewers. The primary outcomes were clinical scores and patient satisfaction. We also investigated the prevalence of complications and the re-operation rate. Ten comparative studies were included (four prospective and six retrospective studies). There were no significant differences between the two procedures in the American Orthopaedic Foot and Ankle Society ankle-hindfoot score, Short Form-36 physical component summary and mental component summary scores, visual analogue scale for pain, and patient satisfaction rate. The risk of re-operation and major surgical complications were significantly increased in the TAA group. The meta-analysis revealed that TAA and AA could achieve similar clinical outcomes, whereas the incidence of re-operation and major surgical complication was significantly increased in TAA. Further studies of high methodological quality with long-term follow-up are required to confirm our conclusions.


Influence of cell cycle phase-specific agents on simian fetal hemoglobin synthesis.
To determine the influence of cell cycle-specific agents on primate hematopoiesis and fetal hemoglobin production, two juvenile cynomolgus monkeys (Macaca fascicularis) were repeatedly bled to maintain their hemoglobins at approximately 6.5 g/dl and fetal hemoglobin levels at 3-5%. Six separate 5-d courses of hydroxyurea at 100 mg/kg per d were then administered over the next 200 d while phlebotomy was continued. These courses of hydroxyurea progressively raised the fetal hemoglobin levels to 17 and 18%, respectively. The drug had very little effect on the frequency of immature erythroid progenitors (BFU-E) in the bone marrow, but caused a marked reduction in the frequency of later progenitors (CFU-E) and a transient fall in the reticulocyte count. Following the courses of hydroxyurea, the number of F cells and the fetal hemoglobin level fell to base line over a period of 4 wk. Two control animals which were not phlebotomized showed no detectable increase in F cells or fetal hemoglobin when treated with the same regimen of hydroxyurea. A 5-d course of 5-azacytidine at 8 mg/kg per d was then given to each of the phlebotomized animals. This produced a more profound, albeit transient, reticulocytopenia, a fall in the CFU-E/BFU-E ratio, and a prompt increase in the fetal hemoglobin to levels even higher than were seen following a single 5-d course of hydroxyurea at 100 mg/kg/d. Subsequently, the animals were given a single dose of vinblastine at 0.4 mg/kg which reduced reticulocytes and CFU-E to the same extent as hydroxyurea; however, vinblastine at this dose had no effect on hemoglobin F (HbF) production. In contrast, when vinblastine was administered to the phlebotomized monkeys as a 5-d course at 0.2 mg/kg/d, prolonged reticulocytopenia followed by dramatic F cell and HbF responses were seen. Combinations of single dose vinblastine and a 5-d course of hydroxyurea were subsequently administered using two different schedules. When the animals received vinblastine on the first day of a 5-d course of hydroxyurea, the F cell response was double that seen following hydroxyurea treatment alone. In contrast, when vinblastine was administered on the final day of hydroxyurea treatment, the magnitude of the F cell response was the same as that which occurred following hydroxyurea treatment alone, but the onset of the rise was delayed for 4 d and HbF/F cell response was much higher. These results establish several important features of the fetal hemoglobin response to cytotoxic agents in the primate model. The response requires accelerated erythropoiesis and is preceded by transient reticulocytopenia. The response is produced by S phase- and M phase-specific agents when given in sufficient doses and at appropriate schedules. Passage of erythrocyte progenitors through M phase appears to be necessary for expression of the effect produced by S phase agents. The fetal hemoglobin response induced by cytotoxic drug administration occurs during the recovery of erythropoiesis following marrow suppression.


Lifestyle modification decreases arterial stiffness in overweight and obese men: dietary modification vs. exercise training.
Obesity and increased arterial stiffness are independent risk factors for cardiovascular disease. Arterial stiffness is increased in obese individuals than in age-matched nonobese individuals. We demonstrated that dietary modification and exercise training are effective in reducing arterial stiffness in obese persons. However, the differences in the effect on arterial stiffness between dietary modification and exercise training are unknown. The purpose of the current study was to compare the effect of dietary modification and aerobic exercise training on arterial stiffness and endothelial function in overweight and obese persons. Forty-five overweight and obese men (48 ± 1 year) completed either a dietary modification (well-balanced nutrient, 1680 kcal/day) or an exercise-training program (walking, 40-60 min/day, 3 days/week) for 12 weeks. Before and after the intervention, all participants underwent anthropometric measurements. Arterial stiffness was measured based on carotid arterial compliance, brachial-ankle pulse wave velocity (baPWV), and endothelial function was determined by circulating level of endothelin-1 (ET-1) and nitric oxide metabolite (nitrites/nitrate as metabolite: NOx). Body mass and waist circumference significantly decreased after both intervention programs. Weight loss was greater after dietary modification than after exercise training (-10.1 ± 0.6 kg vs. -3.6 ± 0.5 kg, p < .01). Although arterial stiffness and the plasma levels of ET-1 and NOx were improved after dietary modification or exercise training, there were no differences in those improvements between the 2 types of interventions. Exercise training improves arterial function in obese men without as much weight loss as after dietary modification.


Reducing Visual Discomfort with HMDs Using Dynamic Depth of Field.
Although head-mounted displays (HMDs) are ideal devices for personal viewing of immersive stereoscopic content, exposure to VR applications on them results in significant discomfort for the majority of people, with symptoms including eye fatigue, headaches, nausea, and sweating. A conflict between accommodation and vergence depth cues on stereoscopic displays is a significant cause of visual discomfort. This article describes the results of an evaluation used to judge the effectiveness of dynamic depth-of-field (DoF) blur in an effort to reduce discomfort caused by exposure to stereoscopic content on HMDs. Using a commercial game engine implementation, study participants report a reduction of visual discomfort on a simulator sickness questionnaire when DoF blurring is enabled. The study participants reported a decrease in symptom severity caused by HMD exposure, indicating that dynamic DoF can effectively reduce visual discomfort.


Preparation of acute hippocampal slices from rats and transgenic mice for the study of synaptic alterations during aging and amyloid pathology.
The rodent hippocampal slice preparation is perhaps the most broadly used tool for investigating mammalian synaptic function and plasticity. The hippocampus can be extracted quickly and easily from rats and mice and slices remain viable for hours in oxygenated artificial cerebrospinal fluid. Moreover, basic electrophysisologic techniques are easily applied to the investigation of synaptic function in hippocampal slices and have provided some of the best biomarkers for cognitive impairments. The hippocampal slice is especially popular for the study of synaptic plasticity mechanisms involved in learning and memory. Changes in the induction of long-term potentiation and depression (LTP and LTD) of synaptic efficacy in hippocampal slices (or lack thereof) are frequently used to describe the neurologic phenotype of cognitively-impaired animals and/or to evaluate the mechanism of action of nootropic compounds. This article outlines the procedures we use for preparing hippocampal slices from rats and transgenic mice for the study of synaptic alterations associated with brain aging and Alzheimer's disease (AD)(1-3). Use of aged rats and AD model mice can present a unique set of challenges to researchers accustomed to using younger rats and/or mice in their research. Aged rats have thicker skulls and tougher connective tissue than younger rats and mice, which can delay brain extraction and/or dissection and consequently negate or exaggerate real age-differences in synaptic function and plasticity. Aging and amyloid pathology may also exacerbate hippocampal damage sustained during the dissection procedure, again complicating any inferences drawn from physiologic assessment. Here, we discuss the steps taken during the dissection procedure to minimize these problems. Examples of synaptic responses acquired in "healthy" and "unhealthy" slices from rats and mice are provided, as well as representative synaptic plasticity experiments. The possible impact of other methodological factors on synaptic function in these animal models (e.g. recording solution components, stimulation parameters) are also discussed. While the focus of this article is on the use of aged rats and transgenic mice, novices to slice physiology should find enough detail here to get started on their own studies, using a variety of rodent models.


A closer look at the recommended criteria for disclosing genetic results: perspectives of medical genetic specialists, genomic researchers, and institutional review board chairs.
Next generation sequencing offers benefit of improved health through knowledge, but comes with challenges, such as inevitable incidental findings (IFs). The applicability of recommended criteria for disclosure of individual results when applied to disclosure of IFs is not well known. The purpose of this study was to examine how medical genetic specialists, genomic researchers, and Institutional Review Board (IRB) chairs perceive the importance of recommended criteria when applied to genetic/genomic IFs. We conducted telephone interviews with medical genetic specialists (genetic counselors, genetic nurses, medical geneticists, laboratory professionals), genomic researchers, and IRB chairs (N = 103). Respondents rated and discussed the importance of nine recommended criteria regarding disclosure of genetic/genomic IFs. Stakeholders agreed the most important criteria for disclosure were: (1) the IF points to a life-threatening condition; (2) there is a treatment; (3) individuals indicate in writing they wanted to be informed of IFs. Criteria rated less important were: analytic validity, high penetrance, association with a young age of onset and relative risk more than 2.0. Respondents indicated that some technical criteria were confusing, and in need of context. Our findings suggest that development of guidelines regarding management of IF include multiple stakeholders' perspectives and be based on a common language.


An unusual marine crocodyliform from the Jurassic-Cretaceous boundary of Patagonia.
Remains of the marine crocodyliform Dakosaurus andiniensis from western South America reveal a lineage that drastically deviated from the skull morphology that characterizes marine crocodyliforms. The snout and lower jaw are extremely robust, short, and high and only bear a few large teeth with serrated edges (resembling those of some terrestrial carnivorous archosaurs). This unusual morphology contrasts with the long and gracile snout and lower jaws bearing numerous teeth, which are present in the closest relatives of D. andiniensis (and interpreted as indicating feeding on small fish or mollusks). Thus, the morphological diversity of pelagic marine crocodyliforms was wider than had been thought.


Effects of Cardiorespiratory Fitness and Obesity on Salivary Secretory IgA and Alpha-Amylase in South African Children.
This study examined whether cardiorespiratory fitness (CRF) and body composition are associated with salivary secretory immunoglobulin A (SIgA), a mucosal immunity marker, and salivary alpha-amylase (sAA), a marker of stress-related sympathetic nervous system (SNS) activity, in South African children. Morning (7:30-8:00 a.m.) saliva samples were collected from 132 children (10.05 ± 1.68 years old, 74 females, 58 males). Body composition, resting blood pressure, and predicted maximal aerobic capacity (VO2max) were determined, and SIgA and sAA were quantified. Obese children had significantly higher sAA compared with overweight and normal weight children (p < 0.01). SIgA secretion rate was significantly lower in obese and overweight vs. normal weight children (p < 0.01). Multiple-linear regression analysis revealed that body mass index (BMI) (p < 0.05) and diastolic blood pressure (DBP) (p < 0.05) were independent predictors of sAA with CRF acting as a mitigator. Age and BMI predicted SIgA secretion rate (p < 0.05) with BMI (p < 0.001) found to be an independent predictor of SIgA secretion rate. Obesity, based on BMI, was associated with elevated SNS activity and lowered mucosal immunity. CRF-mitigated sympathetic activation was not associated with mucosal immunity.


DNA fragmentation index and human papilloma virus in males with previous assisted reproductive technology failures.
This study was designed to evaluate the prevalence of Human Papilloma Virus (HPV) in semen and document the cycle outcomes in couples with previous intra-cytoplasmic sperm injection (ICSI) failures. One hundred and seventeen couples with at least two ICSI attempts were included in the study. HPV infection in semen and DNA fragmentation in samples were analyzed by commercially available kits. The percentage of spermatozoa with fragmented DNA (DNA fragmentation index: DFI) was determined during fluorescence microscopic examination as previously described. The cycle outcomes of couples with or without HPV infected male partners were recorded. According to our results, the prevalence of HPV was 7.7% in asymptomatic males with at least two previous ICSI failures. The increased DFI (>30%) was observed in 82.9% of the cases. In HPV-positive cases significantly lower number of good quality embryos were obtained. The implantation and pregnancy rates were similar in infected and non-infected males (p>0.05). The early miscarriage rate was slightly higher in HPV- positive group (33% vs. 10%, p>0.05). In cases with previous ICSI failures, the prevalence of HPV infection in semen is not higher than previously reported infertile populations. The reproductive outcome might be impaired in HPV-positive semen due to lower number of good quality embryos, which needs to be clarified by further large population-based studies.


Celecoxib, a selective cyclo-oxygenase-2 inhibitor, enhances the response to preoperative paclitaxel and carboplatin in early-stage non-small-cell lung cancer.
Preclinical studies suggest that treatment with a selective cyclo-oxygenase-2 (COX-2) inhibitor may augment the antitumor effects of chemotherapy. In this study, patients with non-small-cell lung cancer (NSCLC) were preoperatively treated with celecoxib in combination with chemotherapy. End points were toxicity, response rates, and measurement of intratumoral levels of prostaglandin E2 (PGE2). In this phase II trial, 29 patients with stages IB to IIIA NSCLC were treated with two preoperative cycles of paclitaxel and carboplatin, as well as daily celecoxib, followed by surgical resection. Levels of PGE2 in the primary tumors and adjacent normal lung tissue were compared in 17 study patients versus 13 controls, who received preoperative paclitaxel/carboplatin without celecoxib. All patients completed preoperative chemotherapy, and 26 completed preoperative celecoxib. The overall clinical response rate was 65% (48% with partial response; 17% with complete response). Grade 3 or 4 neutropenia was observed in 18 patients (62%). Twenty-eight patients were explored and underwent complete resection of their tumors. There were no complete pathologic responses, but seven patients (24%) had minimal residual microscopic disease. The addition of celecoxib to a regimen of paclitaxel and carboplatin abrogated the marked increase in levels of PGE2 detected in primary tumors after treatment with paclitaxel and carboplatin alone. In comparison with historically reported response rates, these data suggest that the addition of a selective COX-2 inhibitor may enhance the response to preoperative paclitaxel and carboplatin in patients with NSCLC. Moreover, treatment with celecoxib 400 mg twice daily was sufficient to normalize the increase in PGE2 levels found in NSCLC patients after treatment with paclitaxel and carboplatin. Confirmatory trials are planned.


Assessing the likely harms to kidney vendors in regulated organ markets.
Advocates of paid living kidney donation frequently argue that kidney sellers would benefit from paid donation under a properly regulated kidney market. The poor outcomes experienced by participants in existing markets are often entirely attributed to harmful black-market practices. This article reviews the medical and anthropological literature on the physical, psychological, social, and financial harms experienced by vendors under Iran's regulated system of donor compensation and black markets throughout the world and argues that this body of research not only documents significant harms to vendors, but also provides reasons to believe that such harms would persist under a regulated system. This does not settle the question of whether or not a regulated market should be introduced, but it does strengthen the case against markets in kidneys while suggesting that those advocating such a system cannot appeal to the purported benefits to vendors to support their case.


The treatment of a large acoustic tumor with fractionated stereotactic radiotherapy.
The treatment of acoustic neuromas (AN) usually involves surgical excision or stereotactic radiosurgery. However, for large AN (mean diameter > 3 cm), stereotactic radiosurgery is rarely used, leaving patients with limited noninvasive treatment options. Recently, the use of fractionated stereotactic radiotherapy (FSRT) has been effective in treating small to medium-sized AN. We present a patient with a large AN treated with FSRT. The patient was a 43-year-old man presenting with imbalance, tinnitus, vertigo, and right-sided hearing decline associated with vomiting and hydrocephalus. Magnetic resonance (MR) imaging revealed a large, 3.8-cm, right cerebellopontine-angle tumor compressing the fourth ventricle. Following right frontal ventriculoperitoneal shunt placement, the patient underwent FSRT for treatment of the tumor. Using the Radionics X-Knife 4.0 3D treatment planning system, a total of 54 Gy was delivered in 1.8-Gy daily fractions with the prescription isodose line of 90%. Treatments were delivered using a dedicated Varian 6/100 linear accelerator, and head immobilization was achieved with the Gill-Thomas-Cosman relocatable stereotactic frame. The patient was subsequently evaluated with serial contrast-enhanced MR imaging. Following FSRT, local control (defined as the absence of tumor progression) was achieved, and treatment was well tolerated. There was no hearing-related, trigeminal, or facial-nerve morbidity following FSRT at 63-month follow-up. Treating a patient with a large AN with FSRT resulted in local tumor control, with no trigeminal nerve, facial nerve, or hearing-related morbidity. These results support FSRT as a potential noninvasive treatment modality for AN some would consider too large for single-fraction stereotactic radiosurgery (SRS).


Extensor indicis proprius opponensplasty for isolated traumatic low median nerve palsy: A case series.
The standard opponensplasty for isolated low median nerve palsy in nonleprosy patients uses the flexor digitorum superficialis of the ring finger. To report the results of extensor indicis proprius (EIP) opponensplasty in 15 consecutive nonleprosy patients with isolated traumatic low median nerve palsy. A retrospective study of the author's cases of EIP opponensplasty for isolated traumatic median nerve palsy over the past 15 years was conducted. The author used the EIP to restore thumb opposition in all cases of isolated median nerve palsies when the following conditions were present: protective sensibility in the median nerve distribution; normal power of EIP; supple hands; and full passive range of opposition with no contracture of the first web space. There were a total of 15 patients with a mean age of 30 years (range 20 to 45 years). They all had traumatic isolated low median nerve palsy with recovery of at least protective sensation and no recovery of opposition. The tendon was harvested just proximal to the extensor expansion, the flexor carpi ulnaris was used as a pulley and the insertion was to the tendon of abductor pollicis brevis. There were no postoperative complications or extension lag of the donor finger. Using previously published criteria, 12 patients experienced excellent results while the remaining three had a good result. In nonleprosy patients with isolated traumatic low median nerve palsy, the results of this transfer are consistent and there is no need to harvest the EIP tendon distal to the extensor expansion because a single insertion to the abductor pollicis brevis is sufficient.


Socio-economic disparities in mortality among the elderly in China.
This longitudinal study of mortality among the elderly (65 and over) in China used a large representative sample to examine the association between mortality and three different socio-economic status (SES) indicators-education, economic independence, and household income per head. The results, while varying depending on the measures used, show that there is strong evidence of a negative association between SES and overall mortality. A cause-specific analysis shows that SES is more strongly related to the reduction of mortality from more preventable causes, such as circulatory disease and respiratory disease, than from less preventable causes such as cancer. We also investigated the effects of three sets of factors that may mediate the observed SES-mortality relationship: support networks, health-related behaviours, and access to health care. The results show that for both overall and cause-specific mortality, access to health care is the most important of the three.


Parameter Estimation for Gene Regulatory Networks from Microarray Data: Cold Shock Response in Saccharomyces cerevisiae.
We investigated the dynamics of a gene regulatory network controlling the cold shock response in budding yeast, Saccharomyces cerevisiae. The medium-scale network, derived from published genome-wide location data, consists of 21 transcription factors that regulate one another through 31 directed edges. The expression levels of the individual transcription factors were modeled using mass balance ordinary differential equations with a sigmoidal production function. Each equation includes a production rate, a degradation rate, weights that denote the magnitude and type of influence of the connected transcription factors (activation or repression), and a threshold of expression. The inverse problem of determining model parameters from observed data is our primary interest. We fit the differential equation model to published microarray data using a penalized nonlinear least squares approach. Model predictions fit the experimental data well, within the 95% confidence interval. Tests of the model using randomized initial guesses and model-generated data also lend confidence to the fit. The results have revealed activation and repression relationships between the transcription factors. Sensitivity analysis indicates that the model is most sensitive to changes in the production rate parameters, weights, and thresholds of Yap1, Rox1, and Yap6, which form a densely connected core in the network. The modeling results newly suggest that Rap1, Fhl1, Msn4, Rph1, and Hsf1 play an important role in regulating the early response to cold shock in yeast. Our results demonstrate that estimation for a large number of parameters can be successfully performed for nonlinear dynamic gene regulatory networks using sparse, noisy microarray data.


Clinician scientist training program: a proposal for training medical students in clinical research.
There is national alarm about a decline in the number of clinician scientists. Most of the proposed solutions have focused on housestaff and junior faculty. We propose a new national program for training medical students in clinical research. This program, coined "Clinician Scientist Training Program" (CSTP), would consist of a combined degree program in medicine (MD) and clinical research (eg, masters in translational research or masters in clinical epidemiology). Students could enroll in the program at any stage during medical school. After 3 years of medical school, students would spend at least 2 years in a combined didactic and mentored clinical research training program and then complete medical school. Students could elect to pursue more prolonged clinical research training toward a combined PhD and MD. The CSTP is designed to meet six critical challenges: 1) engage students early in clinical research training; 2) provide a didactic clinical research curriculum; 3) expose students to several years of mentored clinical research training; 4) promote debt prevention by providing tuition payments during medical education and a stipend during clinical research training; 5) facilitate prolonged exposure to a community of peers and mentors in a program with national and institutional identity and respect; and 6) permit enrollment in the program as students enter medical school or at any stage during medical school. If the success of the Medical Scientist Training Program in training medical students in basic research is a guide, the CSTP could become a linchpin for training future generations of clinician scientists.


Postexercise Hot-Water Immersion Does Not Further Enhance Heat Adaptation or Performance in Endurance Athletes Training in a Hot Environment.
Hot-water immersion (HWI) after training in temperate conditions has been shown to induce thermophysiological adaptations and improve endurance performance in the heat; however, the potential additive effects of HWI and training in hot outdoor conditions remain unknown. Therefore, this study aimed to determine the effect of repeated postexercise HWI in athletes training in a hot environment. A total of 13 (9 female) elite/preelite racewalkers completed a 15-day training program in outdoor heat (mean afternoon high temperature = 34.6°C). Athletes were divided into 2 matched groups that completed either HWI (40°C for 30-40 min) or seated rest in 21°C (CON), following 8 training sessions. Pre-post testing included a 30-minute fixed-intensity walk in heat, laboratory incremental walk to exhaustion, and 10,000-m outdoor time trial. Training frequency and volume were similar between groups (P = .54). Core temperature was significantly higher during immersion in HWI (38.5 [0.3]) than CON (37.8°C [0.2°C]; P < .001). There were no differences between groups in resting or exercise rectal temperature or heart rate, skin temperature, sweat rate, or the speed at lactate threshold 2, maximal O2 uptake, or 10,000-m performance (P > .05). There were significant (P < .05) pre-post differences for both groups in submaximal exercising heart rate (∼11 beats·min-1), sweat rate (0.34-0.55 L·h-1) and thermal comfort (1.2-1.5 arbitrary units), and 10,000-m racewalking performance time (∼3 min). Both groups demonstrated significant improvement in markers of heat adaptation and performance; however, the addition of HWI did not provide further enhancements. Improvements in adaptation appeared to be maximized by the training program in hot conditions.


Evidence that nitric oxide inhibits steroidogenesis in cultured rat granulosa cells.
1. A few studies have shown that nitric oxide may exert cytotoxic and/or steroidogenic effects on cultured ovarian cells but the source of this factor within the ovary remains equivocal. 2. In this study we have investigated the effects of nitric oxide on progesterone secretion, cell viability and cell morphology of cultured rat granulosa/lutein cells and examined whether granulosa cells are an important source of nitric oxide. 3. Only very low or undetectable levels of nitrites were measured in granulosa/lutein-cell-only cultures, although there was a small but significant increase in nitrite release observed in granulosa/ lutein cells obtained from oestrous rats compared with those obtained from proestrous rats. 4. There was a concentration-dependent inhibition of progesterone synthesis in the presence of the nitric oxide donors sodium nitroprusside and S-nitroso-N-acetyl-penicillamine which corresponded with an increased concentration of nitrite accumulation in the culture medium. 5. High concentrations of nitrites were measured in the medium of granulosa/lutein cells co-cultured with peritoneal macrophages and progesterone synthesis was inhibited. This effect of the macrophages was partially reversed by inhibitors of nitric oxide synthesis, aminoguanidine, NG-methyl-L-arginine and NG-L-arginine-methyl-ester, and the reversal of inhibition was inversely proportional to the concentration of nitrites measured in the medium. Dose-response curves for the three drugs on the inhibition of nitrite accumulation in macrophage cultures were obtained. 6. The nitric oxide scavenger c-PTIO [2-(4-carboxy-phenyl) -4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide.potassium salt] partially reversed the effects of S-nitroso-N-acetyl-penicillamine and macrophages on progesterone synthesis in granulosa/ lutein cells. 7. With the exception of the high dose of sodium nitroprusside, there was no evidence that any of the drugs reduced cellular viability, as assessed by measurement of cellular dehydrogenases and Trypan Blue exclusion, although high concentrations of nitrite in the culture medium derived either from the nitric oxide donors or macrophages were associated with a loss of morphological luteinization. 8. Based on the available evidence, we suggest that nitric oxide can inhibit steroidogenesis and that in vivo the source of nitric oxide may be from macrophages, which invade the ovary during the periovulatory period, and/or from endothelial cells of ovarian blood vessels.


Infections, toxic chemicals and dietary peptides binding to lymphocyte receptors and tissue enzymes are major instigators of autoimmunity in autism.
Similar to many complex autoimmune diseases, genetic and environmental factors including diet, infection and xenobiotics play a critical role in the development of autism. In this study, we postulated that infectious agent antigens such as streptokinase, dietary peptides (gliadin and casein) and ethyl mercury (xenobiotic) bind to different lymphocyte receptors and tissue enzyme (DPP IV or CD26). We assessed this hypothesis first by measuring IgG, IgM and IgA antibodies against CD26, CD69, streptokinase (SK), gliadin and casein peptides and against ethyl mercury bound to human serum albumin in patients with autism. A significant percentage of children with autism developed anti-SK, anti-gliadin and casein peptides and anti-ethyl mercury antibodies, concomitant with the appearance of anti-CD26 and anti-CD69 autoantibodies. These antibodies are synthesized as a result of SK, gliadin, casein and ethyl mercury binding to CD26 and CD69, indicating that they are specific. Immune absorption demonstrated that only specific antigens, like CD26, were capable of significantly reducing serum anti-CD26 levels. However, for direct demonstration of SK, gliadin, casein and ethyl mercury to CD26 or CD69, microtiter wells were coated with CD26 or CD69 alone or in combination with SK, gliadin, casein or ethyl mercury and then reacted with enzyme labeled rabbit anti-CD26 or anti-CD69. Adding these molecules to CD26 or CD69 resulted in 28-86% inhibition of CD26 or CD69 binding to anti-CD26 or anti-CD69 antibodies. The highest % binding of these antigens or peptides to CD26 or CD69 was attributed to SK and the lowest to casein peptides. We, therefore, propose that bacterial antigens (SK), dietary peptides (gliadin, casein) and Thimerosal (ethyl mercury) in individuals with pre-disposing HLA molecules, bind to CD26 or CD69 and induce antibodies against these molecules. In conclusion, this study is apparently the first to demonstrate that dietary peptides, bacterial toxins and xenobiotics bind to lymphocyte receptors and/or tissue enzymes, resulting in autoimmune reaction in children with autism.


Microsporidia: Why Make Nucleotides if You Can Steal Them?
Microsporidia are strict obligate intracellular parasites that infect a wide range of eukaryotes including humans and economically important fish and insects. Surviving and flourishing inside another eukaryotic cell is a very specialised lifestyle that requires evolutionary innovation. Genome sequence analyses show that microsporidia have lost most of the genes needed for making primary metabolites, such as amino acids and nucleotides, and also that they have only a limited capacity for making adenosine triphosphate (ATP). Since microsporidia cannot grow and replicate without the enormous amounts of energy and nucleotide building blocks needed for protein, DNA, and RNA biosynthesis, they must have evolved ways of stealing these substrates from the infected host cell. Providing they can do this, genome analyses suggest that microsporidia have the enzyme repertoire needed to use and regenerate the imported nucleotides efficiently. Recent functional studies suggest that a critical innovation for adapting to intracellular life was the acquisition by lateral gene transfer of nucleotide transport (NTT) proteins that are now present in multiple copies in all microsporidian genomes. These proteins are expressed on the parasite surface and allow microsporidia to steal ATP and other purine nucleotides for energy and biosynthesis from their host. However, it remains unclear how other essential metabolites, such as pyrimidine nucleotides, are acquired. Transcriptomic and experimental studies suggest that microsporidia might manipulate host cell metabolism and cell biological processes to promote nucleotide synthesis and to maximise the potential for ATP and nucleotide import. In this review, we summarise recent genomic and functional data relating to how microsporidia exploit their hosts for energy and building blocks needed for growth and nucleic acid metabolism and we identify some remaining outstanding questions.


On the efficiency of angular intraprediction.
Angular intraprediction (AIP) is a coding tool that has been incorporated into the video coding standards H.264/AVC (Advanced Audio Coding) and High Efficient Video Coding. In this paper, we study how the efficiency of AIP depends on its prediction parameters. To carry out this paper, we first theoretically analyze the variance of the error incurred when a perfectly directional signal is predicted in a certain direction. The results of this analysis are then used to study the efficiency of AIP when it is applied to a distribution of directions. To facilitate mathematical derivations, we make several assumptions about the signal and the prediction process, and we use some approximations. This allows us to obtain simple expressions for the variance of the AIP prediction error as a function of signal and prediction parameters. Finally, we compare our theoretical results with the results obtained from the prediction of images containing rectilinear edges. This comparison shows that our theoretical expressions follow the main trends of the experimental results except when AIP is performed with a very high accuracy.


Cycling injuries among junior high school children in Taiwan.
We surveyed the injuries sustained by 197 junior high school students (aged 12 to 15 years) while riding a bicycle within the previous 12 months, together with the same number of controls matched according to age and sex. The case sites and control sites, selected from routes control subjects would have taken if pursuing the same purpose as the case subject at the time of the accident, were also investigated. Male students and older students were found to be at higher risk. One-third of the injuries occurred while the students were traveling to school. Nearly 40% of the accidents happened between 15:00 and 19:00, and 52% occurred during the summer months. More than half of the accidents took place near street corners. Injuries were mainly (89%) to one of the limbs. Injuries were more severe among those with head injuries. None of the injured children wore a helmet while cycling. Most injuries (83%) were due to collisions with another vehicle. Motorcycles were involved in the collisions most often. When compared with the total number of registered vehicles, the proportion of trucks, light commercial vans, and taxis involved in the crashes was significantly higher. Drivers of the vehicles involved were primarily males, evenly distributed across all age groups. The volume of traffic was marginally heavier at case sites, but estimated average speeds of vehicles were similar between case and control sites. More obstacles, such as illegally parked vehicles and vendors' stalls, were found at case sites. In addition to wearing a helmet, other prevention strategies should be considered.